Measles remains a major worldwide health problem and recent outbreaks of measles in the US have involved many previously vaccinated individuals and infants younger than 15 months. A second dose of vaccine is now recommended, but effective immunization of young children remains a problem. Immunization of infants as young as 4-6 months has been successful using a 10-100-fold higher dose of vaccine, but such immunization has been associated with a poorly understood increase in susceptibility to subsequent infections and must be abandoned as a strategy for improving the vaccine and lowering the age of immunization. An inactivated vaccine was one of the earliest measles vaccines introduced but was associated with development of a severe form of measles, "atypical measles". Failure to understand the pathogenesis of atypical measles continues to impede the development of newer vaccines. Measurements of T cell immunity induced by measles suggest an early CD8-mediated cytotoxic response with little evidence of induction of classical delayed type hypersensitivity. We suggest that there may be fundamental differences in the types of T cell responses induced by live and inactivated virus. In this proposal we plan to determine the pathogenesis of atypical measles and characterize the immune responses to prototype and new vaccines. The aims of the proposal are: (1) To characterize measles virus-specific T cell clones from individuals with previous measles, live vaccine and inactivated vaccine for cytokine synthesis and T cell receptor usage. (2) To determine the effects of live and inactivated measles virus on the function of monocytes. (3) To characterize the measles virus-specific T and B cell responses of rhesus macaques to inactivated and live measles virus vaccines and assess susceptibility of immunized animals to challenge with wildtype virus. (4) To compare the measles virus-specific T and B cell responses of nonhuman primates to newer measles vaccines including Edmonston-Zagreb, canarypox/measles and vaccinia/measles. (5) To develop a plasmid DNA vaccine for measles and characterize the immune responses to the vaccine in mice and monkeys.